Broad-spectrum anti-infective peptides

Abstract

Provided herein are anti-infective peptides and uses thereof. Such anti-infective peptides are useful against bacteria and viruses. Also provided herein are compositions comprising said anti-infective peptides.

Description

[0001]This application is a national stage of International Patent Application No. PCT / SG2016 / 050291, filed on Jun. 24, 2016, which claims the benefit of U.S. Provisional Application No. 62 / 184,354, filed Jun. 25, 2015, each of which is incorporated herein by reference in its entirety.[0002]This application incorporates by reference a Sequence Listing submitted with this application as text file entitled “SeqListing_14312_001_228” created on Jun. 22, 2016 and having a size of 23,659 bytes.1. INTRODUCTION[0003]Provided herein are anti-infective peptides and uses thereof. Such anti-infective peptides are useful against bacteria and viruses. Also provided herein are compositions comprising said anti-infective peptides.2. BACKGROUND[0004]Antibiotics are the most common drug class to treat bacterial infections and are a key part of the pharmaceutical industry. There are high annual expenses for antibiotics of more than US$10 billion in the United States. The global expenses are much grea...

AI Technical Summary

Problems solved by technology

There are high annual expenses for antibiotics of more than US$10 billion in the United States.

This high usage of antibiotics is a major public health problem because it creates drug-resistant bacteria.

These are bacteria that cannot be killed by common antibiotics and they can cause serious infections that spread in the body.

There is significant concern about bacterial resistance, especially multidrug-resistant bacterial strains that are called “super bacteria.” The biggest issue is that infections caused by these drug-resistant bacteria cannot be treated by common antibiotics.

The market potential for treating drug-resistant bacterial infections is very large.

While MRSA skin infections are merely one example, the numbers from this case alone support that there are significant human and economic costs from infections caused by multidrug-resistant bacterial strains.

The development of new antibiotics is a low priority for many companies because the treatment time is short and it is difficult to identify new classes of antibiotics.

It is difficult to find new classes of antibiotics because it was already significantly researched.

There are also many generic antibiotics available over the counter and companies worry that these drugs create high competition that could decrease possible profits from a new antibiotic.

It is very expensive and takes a long time to develop a new drug so that drug should have patent protection and fill a need that is unmet by generic antibiotics.

In addition, it has been difficult to get new antibiotics approved by regulatory agencies, including the United States Food and Drug Administration (FDA).

There are a limited number of topical antibiotics, and all classes of antibiotics have problems with resistant strains quickly emerging.

One alternative is antimicrobial peptides that are membrane-active but these peptides have not found wide application because they have relatively expensive production costs (due to lengthy amino acid sequences) and there were two failed clinical trials in the 90's which led already risk-averse pharmaceutical companies to stick with small molecule antibiotics.

However, these peptides completely lack antibacterial activity.

However, topical antibiotics have serious problems because bacteria can easily mutate.

Other types of antibiotics used to treat MRSA skin infections require intravenous administration or have questionable efficacy.

Given the accelerating pace of viral spread worldwide, the lack of countermeasures to prevent or blunt ZIKV infection is a major challenge, and there are currently no approved vaccines or therapies (Malone et al., PLoS Negl Trop Dis 10, e0004530 (2016)).

However, the identification of an antiviral agent that destabilizes ZIKV particles in the context of preventing virus entry remains elusive, particularly one which is both therapeutically selective and broadly applicable.

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